Supranutritive selenium (Se) in combination with glucoraphanin (GRA) maximizes the expression of Nrf2-regulated genes in the colon of rats
Abstract
The isothiocyanate Sulforaphane (SFN), the hydrolysis product of GRA, activates Nrf2 which induces chemopreventive phase 2 enzymes. An unexpected Nrf2 target is the Se-dependent gastrointestinal glutathione peroxidase 2 (GPx2) [1] to which anti-carcinogenic functions have been attributed [2]. These observations led to the hypothesis that Se and SFN synergistically act in cancer prevention [3]. We therefore studied whether Se and GRA also cooperate in the induction of other phase 2 enzymes [4-7]. 48 weaned albino rats were assigned to 4 groups of 12 and fed diets with the recommended or a supranutritive Se level (150 and 450 µg Se as selenate/kg diet), either without GRA (C150 and C450) or in combination with 850 µmol GRA/kg diet (G150 and G450) for 8 weeks. Colonic Nrf2 target genes, Nrf2 itself, NAD(P)H:quinone oxidoreductase 1 (NQO1), and glutathione-S-transferases (GSTs) were measured by real time-RT-PCR. Nrf2 expression only slightly responded to supranutritive Se (C450), but was significantly increased by GRA with a maximum expression in G450 rats (Table). Whereas GPx2 and GSTt2ď€ RNA only responded to GRA, induction of NQO1 and GSTpi1 by GRA was enhanced by supranutritive Se.
Table: Influence of Se and GRA on colonic Nrf2 targets Group C150 C450 G150 G450
Gene
Nrf2 1.00±0.24a 1.36±0.36ab 1.80±0.12bc 2.12±0.26c
GPx2 1.00±0.13a 1.17±0.30ab 1.41±0.22ab 1.71±0.14b
NQO1 1.00±0.16a 1.29±0.25a 2.21±0.40b 3.40±0.29c
GSTpi11.00±0.12a 1.96±0.33b 2.35±0.29b 3.35±0.25c
GSTt2 1.00±0.13a 1.08±0.08a 1.77±0.24bc 2.29±0.41c Unlike small letters within a line display significant differences between means (P<0.05)
We conclude that slightly supranutritive Se may support GRA-mediated induction of certain phase 2 enzymes.
References
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